Haemochromatosis

Question 1

summarise haemochromatosis?

Answer 1

bronzed diabetic with hepatomegaly, deranged LFTs

Low transferrin, high ferritin, TIBC low

Question 2

define haemochromatosis?

Answer 2

Autosomal recessive disease caused by defect in HFE gene.

Multisystem disorder of dysregulated dietary iron absorption and increased iron release from macrophages.

Advanced cases may present with life-threatening complications-> cirrhosis, hepatocellular cancer, diabetes, and heart disease.

The mutation associated with haemochromatosis is highly prevalent in white populations but the disorder has variable penetrance.

Question 3

summarise the epidemiology of haemochromatosis?

Answer 3

rare

more frequent in middle aged men than women->tends to present later in women ( menstrual blood loss is protective)

Question 4

what are the risk factors for haemochromatosis?

Answer 4

middle aged

man gender

white ancestry

family history

supplemental iron

Question 5

outline the aetiology of haemochromatosis?

Answer 5

Iron absorbed in duodenum where it is stored intracellullarly bound to ferritin or transported out of the cells by ferroportin, then binds to transferrin in the blood. Hepcidin is a protein that inhibit ferroportin, thereby regulating the amount of iron entering the blood. 90% of cases of HH are caused by a mutation that leads to a deficiency to hepcidin, resulting in unregulated absorption of iron in the intestines.

the genetic penetrance of haemochromatosis is complex - not everyone who is homozygous will develop the clinical disease

Question 6

what are the presenting symptoms and signs of haemochromatosis?

Answer 6

often asymptomatic until late stages-> symptoms start at 40-60 yrs

EARLY SYMPTOMS ARE VAGUE

• fatigue
• weakness
• lethargy
• arthropathy
• erectile dysfunction
• heart problems

=> MAY BE INCIDENTAL FINDING ( LFTs, serum ferritin)

LATE SYMPTOMS 
- diabetes meltius 
- bronzed skin-> grey/ brown with slate- grey patches in mouth 
- hepatomegaly 
- loss of libido 
- amenorrhoea 
- hypogonadism 
- cirrhosis 
 cardiac- arrhythmias and cardiomyopathy

Question 7

why is serum ferritin not the best test?

Answer 7

not specific as it is an acute phase protein ( increases in infection etc)

Question 8

what is the first investigation for haemochromatosis?

Answer 8

HAEMATINICS

• SERUM FERRITIN HIGH
• TRANSFERRIN SATURATION IS HIGH
• transferrin is low
• TIBC is low

Question 9

what tests hsould you consider for haemochromatosis?

Answer 9

• Tests to exclude other causes of high ferritin:
○ CRP - inflammation
○ Chronic alcohol consumption
○ ALT - liver necrosis

• LFTs
• Hormones tested as raised ferritin can cause hypogonadism (low Testosterone, FSH + LH)
• Other investigations for abnormal liver function (e.g. hepatitis serology)
• Bone Densitometry - do if have concomitant predisposing factors to osteoporosis
• Genetic testing e.g. HFE mutation analysis
• Liver MRI for Fe overload

• Liver biopsy (rarely required) – Perl’s stain quantifies iron loading and assesses disease severity.
ECG/ECHO if cardiomyopathy suspected

Question 10

summarise a person with haemochromatosis?

Answer 10

Bronzed diabetic with hepatomegaly, derranged LFTs

low transferrin, high ferritin, TIBC low